Structural change, convergence and networks: theoretical and empirical analyses

The dissertation consists of three chapters that study topics related to structural change, spatial and network data. The first chapter considers the problem of testing for a structural change in the spatial lag parameter in a panel model. We propose a likelihood ratio test of the null hypothesis of no change against the alternative hypothesis of a single change. The limiting distribution of the test is derived under the null hypothesis when the number of time periods is large. We also propose a break-date estimator to determine the location of the change point following evidence against the null hypothesis. We present Monte Carlo evidence to show that the proposed procedure performs well in finite samples. We use US state budget data to investigate changes in budget spillovers and the interdependence of fiscal policy within US states. The second chapter proposes a theory of cross-country migration in the form of labor mobility based on regional and sectoral productivity shocks in a multi-country, multi-sector setting. The productivity model when applied to US state data explains both the nominal and relative flow of workers across the U.S. well, which is taken as the frictionless benchmark. On the other hand, when applied to Europe the model explains the relative flow network well, but predicts a higher nominal flow. This missing mass of migrants is explained by socio-cultural-political barriers. We use dyadic regressions to assess the effects of institutional and cultural "distance" between countries in explaining the "European immobility puzzle". The third chapter shows that the "iron-law" of convergence (2\%) still holds for the world. We document a structural break in Africa's convergence rate and argue that Africa was not converging before 2000. The world convergence rate before 2000 was driven by Asian and Latin American countries. We show that recent institutional and infrastructural developments have led the African countries on the path of "catching up". We use Least-Absolute-Shrinkage-and-Selection-Operator (LASSO) to select the variables and a double selection method to estimate the treatment effect in a partially linear model. We compare LASSO variable selections with those obtained using Gradient-Boosting-Method (GBM) and Random Forest

Study on epidemiology of endometriosis in North East India

Background: Endometriosis is the presence of endometrial glands and/or stroma outside the uterus, predominantly in   reproductive age. The prevalence is around 10% in women of reproductive age and is caused by combination of multiple genetic and environmental factors. Characterization of endometriosis can be learnt from epidemiological factors of the patients which influence on disease development and thus helpful in clinical diagnosis. Histological pictures after surgery may vary considerably and sometimes over diagnosis of the disease is not uncommon. The purpose of the study was to study the epidemiology of endometriosis in North East population of India and correlation of clinical and histopathological diagnosis. Methods: It was a hospital based observational descriptive study carried out in Department of Obstetrics and Gynecology, AMCH, Dibrugarh, Assam, India.  Detailed history and clinical presentations were elicited and relevant investigations were done. Operative findings and biopsy reports were correlated. All the findings were tabulated and statistically analyzed. Results: Women in age group 30-39 years (48.31%) with mean BMI of 24.44±4.06 kg/m2, nulliparous (31.46%) or para 1(33.71%) formed the majority of study population. Majority had early age at menarche (11.45±1.24), irregular cycles, shorter cycle length, longer duration of flow. Majority (79.78%) had dysmenorrhea followed by dyspareunia (59.55%). Only 62.92% had biopsy proven endometriosis. Conclusions: Epidemiological factors and clinical presentations guide in diagnosing endometriosis and should be given importance. Clinical diagnosis of endometriosis may not always correlate with histopathologic diagnosis and many other pathologies mimic endometriosis

Evaluation of the therapeutic efficacy of Vitex agnus-castus extract on cisplatin-induced hematotoxicity in female Wistar rats

Background and Aim: Cisplatin (CP) is a preferred drug for cancer treatment but it has dose-dependent side effects. Vitex agnus-castus (VAC) berry extract has antioxidant, free-radical scavenging, and anti-inflammatory activities. This study explored the mitigating effects of VAC extract (VACE) on acute hematotoxicity induced by CP in female Wistar rats. Materials and Methods: Female Wistar rats (n = 30) were randomly divided into five groups (n = 6/group). The normal control (NC) group received no treatment. The CP control group received CP (7 mg/kg.b.w. ip, single dose) and the drug control group (VACE-650) received VACE (650 mg/kg b.w. oral, daily) for 7 days. Both groups received a single dose of CP (7 mg/kg b.w. ip), followed by 350 and 650 mg/kg.b.w. of VACE daily orally (CPVACE-350 and CPVACE-650 groups, respectively) for 7 days. Results: After a single dose of CP (7 mg/kg b.w.), the red blood cells (RBC), hematocrit (HCT), white blood cells (WBC), and platelets significantly decreased. In the VAC-350 group, the reduction in total WBC count was less than that in the VAC-650 group on the 3rd day. The RBC and HCT values of the VACE groups were better than that of the CP control, but the VACE-350 treatment group showed significant improvement only on the 3rd day. Conclusion: Our findings showed that VACE can mitigate CP-induced damage to peripheral blood cells at lower doses

Universal and language-specific connected speech characteristics of bilingual speakers with Alzheimer’s Disease: insights from case studies of structurally distinct languages

Purpose: Connected speech analysis has been effectively utilized for the diagnosis and disease monitoring of individuals with Alzheimer’s Disease (AD). Existing research has been conducted mostly in monolingual English speakers with a noticeable lack of evidence from bilinguals and non-English speakers, particularly in non-European languages. Using a case study approach, we characterized connected speech profiles of two Bengali-English bilingual speakers with AD to: determine the universal features of language impairments in both languages, identify language-specific differences between the languages, and explore language impairment characteristics of the participants with AD in relation to their bilingual language experience. Method: Participants included two Bengali-English bilingual speakers with AD and a group of age-, gender-, education- and language-matched neurologically healthy controls. Connected speech samples were collected in L1 (Bengali) and L2 (English) using a novel storytelling task (i.e., “Frog, where are you?”). These samples were analyzed using an augmented Quantitative Production Analysis and Correct Information Unit analyses for productivity, fluency, syntactic and morpho-syntactic features, lexical and semantic characteristics. Results: Irrespective of the language, AD impacted speech productivity (speech rate and fluency) and semantic characteristics in both languages. Unique language-specific differences were noted on syntactic measures (reduced sentence length in Bengali), lexical distribution (fewer pronouns and absence of reduplication in Bengali) and inflectional properties (no difficulties with noun or verb inflections in Bengali). Among the two participants with AD, the individual who showed lower proficiency and usage in L2 (English) demonstrated reduced syntactic complexity and morpho-syntactic richness in English. Conclusion: Evidence from these case studies suggest that language impairment features in AD are not universal across languages, particularly in comparison to impairments typically associated with language breakdowns in English. This study underscores the importance of establishing connected speech profiles in AD for non-English speaking populations, especially for structurally different languages. This would in turn lead to the development of language-specific markers that can facilitate early detection of language deterioration and aid in improving diagnosis of AD in individuals belonging to underserved linguistically diverse populations

Connected speech characteristics of Bengali speakers with Alzheimer’s Disease: evidence for language-specific diagnostic markers

Background & Aim: Speech and language characteristics of connected speech provide a valuable tool for identifying, diagnosing and monitoring progression in Alzheimer’s Disease (AD). Our knowledge of linguistic features of connected speech in AD is primarily derived from English speakers; very little is known regarding patterns of linguistic deficits in speakers of other languages, such as Bengali. Bengali is a highly inflected pro-drop language from the Indo-Aryan language family. It is the seventh most spoken language in the world, yet to date, no studies have investigated the profile of linguistic impairments in Bengali speakers with AD. The aim of this study was to characterize connected speech production and identify the linguistic features affected in Bengali speakers with AD. Methods: Participants were six Bengali speaking AD patients and eight matched controls from the urban metropolis, Kolkata, India. Narrative samples were elicited in Bengali using the Frog Story. Samples were analyzed using the Quantitative Production Analysis and the Correct Information Unit analyses to quantify six different aspects of speech production: speech rate, structural and syntactic measures, lexical measures, morphological and inflectional measures, semantic measures and measure of spontaneity and fluency disruptions. Results & Conclusions: In line with the extant literature from English speakers, the Bengali AD participants demonstrated decreased speech rate, simplicity of sentence forms and structures, and reduced semantic content. Critically, differences with English speakers’ literature emerged in the domains of Bengali specific linguistic features, such as the pro-drop nature of Bengali and its inflectional properties of nominal and verbal systems. Bengali AD participants produced fewer pronouns, which is in direct contrast with the overuse of pronouns by English AD participants. No obvious difficulty in producing nominal and verbal inflections was evident. However, differences in the type of noun inflections were evident; these were characterized by simpler inflectional features used by AD speakers. This study represents the first of its kind to characterize connected speech production in Bengali AD participants and is a significant step forward towards the development of language-specific clinical markers in AD. It also provides a framework for cross-linguistic comparisons across structurally distinct and under-explored languages

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Molecular Cloning and Expression Analysis of fushi tarazu Factor 1 in the Brain of Air-Breathing Catfish, Clarias gariepinus

BACKGROUND: Fushi tarazu factor 1 (FTZ-F1) encodes an orphan nuclear receptor belonging to the nuclear receptor family 5A (NR5A) which includes adrenal 4-binding protein or steroidogenic factor-1 (Ad4BP/SF-1) and liver receptor homologue 1 (LRH-1) and plays a pivotal role in the regulation of aromatases. METHODOLOGY/PRINCIPAL FINDINGS: Present study was aimed to understand the importance of FTZ-F1 in relation to brain aromatase (cyp19a1b) during development, recrudescence and after human chorionic gonadotropin (hCG) induction. Initially, we cloned FTZ-F1 from the brain of air-breathing catfish, Clarias gariepinus through degenerate primer RT-PCR and RACE. Its sequence analysis revealed high homology with other NR5A1 group members Ad4BP/SF-1 and LRH-1, and also analogous to the spatial expression pattern of the latter. In order to draw functional correlation of cyp19a1b and FTZ-F1, we analyzed the expression pattern of the latter in brain during gonadal ontogeny, which revealed early expression during gonadal differentiation. The tissue distribution both at transcript and protein levels revealed its prominent expression in brain along with liver, kidney and testis. The expression pattern of brain FTZ-F1 during reproductive cycle and after hCG induction, in vivo was analogous to that of cyp19a1b shown in our earlier study indicating its involvement in recrudescence. CONCLUSIONS/SIGNIFICANCE: Based on our previous results on cyp19a1b and the present data, it is plausible to implicate potential roles for brain FTZ-F1 in ovarian differentiation and recrudescence process probably through regulation of cyp19a1b in teleosts. Nevertheless, these interactions would require primary coordinated response from ovarian aromatase and its related transcription factors

Developing Standard Treatment Workflows—way to universal healthcare in India

Primary healthcare caters to nearly 70% of the population in India and provides treatment for approximately 80–90% of common conditions. To achieve universal health coverage (UHC), the Indian healthcare system is gearing up by initiating several schemes such as National Health Protection Scheme, Ayushman Bharat, Nutrition Supplementation Schemes, and Inderdhanush Schemes. The healthcare delivery system is facing challenges such as irrational use of medicines, over- and under-diagnosis, high out-of-pocket expenditure, lack of targeted attention to preventive and promotive health services, and poor referral mechanisms. Healthcare providers are unable to keep pace with the volume of growing new scientific evidence and rising healthcare costs as the literature is not published at the same pace. In addition, there is a lack of common standard treatment guidelines, workflows, and reference manuals from the Government of India. Indian Council of Medical Research in collaboration with the National Health Authority, Govt. of India, and the WHO India country office has developed Standard Treatment Workflows (STWs) with the objective to be utilized at various levels of healthcare starting from primary to tertiary level care. A systematic approach was adopted to formulate the STWs. An advisory committee was constituted for planning and oversight of the process. Specialty experts' group for each specialty comprised of clinicians working at government and private medical colleges and hospitals. The expert groups prioritized the topics through extensive literature searches and meeting with different stakeholders. Then, the contents of each STW were finalized in the form of single-pager infographics. These STWs were further reviewed by an editorial committee before publication. Presently, 125 STWs pertaining to 23 specialties have been developed. It needs to be ensured that STWs are implemented effectively at all levels and ensure quality healthcare at an affordable cost as part of UHC

Significant benefits of AIP testing and clinical screening in familial isolated and young-onset pituitary tumors

Context Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene are responsible for a subset of familial isolated pituitary adenoma (FIPA) cases and sporadic pituitary neuroendocrine tumors (PitNETs). Objective To compare prospectively diagnosed AIP mutation-positive (AIPmut) PitNET patients with clinically presenting patients and to compare the clinical characteristics of AIPmut and AIPneg PitNET patients. Design 12-year prospective, observational study. Participants & Setting We studied probands and family members of FIPA kindreds and sporadic patients with disease onset ≤18 years or macroadenomas with onset ≤30 years (n = 1477). This was a collaborative study conducted at referral centers for pituitary diseases. Interventions & Outcome AIP testing and clinical screening for pituitary disease. Comparison of characteristics of prospectively diagnosed (n = 22) vs clinically presenting AIPmut PitNET patients (n = 145), and AIPmut (n = 167) vs AIPneg PitNET patients (n = 1310). Results Prospectively diagnosed AIPmut PitNET patients had smaller lesions with less suprasellar extension or cavernous sinus invasion and required fewer treatments with fewer operations and no radiotherapy compared with clinically presenting cases; there were fewer cases with active disease and hypopituitarism at last follow-up. When comparing AIPmut and AIPneg cases, AIPmut patients were more often males, younger, more often had GH excess, pituitary apoplexy, suprasellar extension, and more patients required multimodal therapy, including radiotherapy. AIPmut patients (n = 136) with GH excess were taller than AIPneg counterparts (n = 650). Conclusions Prospectively diagnosed AIPmut patients show better outcomes than clinically presenting cases, demonstrating the benefits of genetic and clinical screening. AIP-related pituitary disease has a wide spectrum ranging from aggressively growing lesions to stable or indolent disease course